Month: January 2015

Suicide Gene Therapy: The Genetic “Kill Switch”

What it is?

Suicide gene therapy is based on the introduction of a viral or a bacterial gene into tumor cells, which allows the conversion of a non-toxic compound into a lethal drug.

Basically suicide gene therapy also known as Gene Directed Enzyme/Prodrug therapy (GDEPT) or as Gene Prodrug Activation Therapy (GPAT) uses viral vectors to deliver suicide genes into tumor cells which possess the enzyme that converts prodrug to active metabolites, it increases the toxicity level several fold inside the tumor whereas the vast majority of the host cells are unaffected. Thus it accomplishes the same end goal of chemotherapy treatments, but by different means. While chemotherapy targets all of the body’s rapidly dividing cells with the intention of killing cancer cells, suicide gene therapy delivers a cancer-killing drug solely to tumors. This bypasses chemotherapy side effects like hair loss and nausea, which are caused by collateral damage to non-cancerous cells.

How it works?

There are several suicide gene therapies. Among them Herpes Simplex Virus thymidine kinase (HSV-tk) and Cytodine Deaminase (CD) are important. The Herpes Simplex Virus deposits a gene into the cancer cells that causes them to produce a special enzyme. Once the virus triggers production of the enzyme, doctors initiate step two by injecting the patient with a unique type of chemotherapy drug called a prodrug. Suicide gene therapy typically uses ganciclovir (GCV) and its nucleoside analogs (acyclovir etc). When administered, GCV and other prodrugs are nontoxic, and thus cause no harm to healthy cells.

But when GCV comes in contact with the special enzyme, the prodrug turns highly toxic. This starts a natural biological process called programmed cell death, which causes cells to commit suicide. Because HSV-tk and CD are not present in any of the body’s healthy cells, the prodrug only destroys cancer cells that were genetically altered by the virus.

Although only a limited number of tumor cells will take in HSV-tk or CD from the virus, the activated prodrug is passed on to neighboring cells through what doctors call the bystander effect. Further, cells that destroy themselves as a response to treatment attract immune cells that clear the tumor site of dead and dying cancer cells.

Limitations of (HSV-tk)-GCV system

This HSV-tk system suffers from limitations which include (i) the potential for production of inactive catalytic molecules due to the utilization of alternative splicing sites, (ii) the potential immunogenicity of the viral enzyme, (iii) the potential need to administer GCV to control cytomegalovirus infections (a complication often encountered in allo-HSCT) and thus cause unintended elimination of HSV/Tk-engineered cells, and (iv) the requirement for active cell division in order to mediate cell death, which takes time and renders the system less effective for use in post mitotic cells. Moreover, major improvements are needed in vector design to enhance targeting and delivery of suicide genes.

Live and Let Die: A New Suicide Gene Therapy

Despite of the limitations associated with HSV/tk-GCV system suicide gene therapy holds enormous potential in the eye of the researchers which is evident from the research done on combining suicide gene therapy with other treatments, improving the bystander effect and finding the optimal method for delivering GCV and the HSV-tk gene. One such example is iCasp9 (a late executor of the intrinsic pathway of apoptosis, leading to DNA fragmentation and rapid cell death) which represents more than a simple upgrade of the HSV/Tk-GCV system as it is not dependent on DNA synthesis as is HSV/Tk-GCV, allowing application in non-replicating cells. It involves dimerization of the subunits which is induced by addition of a biologically inert small molecule (AP1903) that has been shown in clinical studies to be well tolerated. Dimerization of iCasp9 activates one of the last steps in the apoptotic cascade, resulting in rapid cell death—as soon as 30 minutes after administration of the activator.

The field of suicide gene therapy is rapidly maturing and will no doubt be part of the future of cancer therapeutics. In addition, combination of Gene & Cell therapy approaches like “chimeric antigen receptors” or CARs for short also hold great promise for increasing the effectiveness of current chemotherapeutic treatment regimens.

For more information on Gene Therapy Reports for various Therapeutic areas contact us at: info@delveinsight.com.

Immense Growth Potential in the Gene Therapy Market!

DelveInsight has launched its Gene Therapy Report: “Gene Therapy Insight: Pipeline Assessment, Market Trend, Technology and Competitive Landscape”. These Reports are the outcome of very best analytical abilities and diligent market research amalgamated with opinions of gene therapy industry experts. The report uncovers the potential of global Gene Therapy Market with insights into 15 Therapy Areas with collective pipeline of more than 300 gene therapies and the companies at their forefront.

Report Summary

These reports provide information across the gene therapy value chain covering gene therapy profiles core insights, pre-clinical data, clinical data, technology details, funding and licensing opportunities. The Report provides the gene therapy targets which are close to 190 with the target gene name, localization of gene, molecular function of target with descriptive mechanism of action. Using the propriety DelveInsight Competitive Matrix models, the report also provides the first in class market analytics providing predictive analysis of early market winners of the clinical therapies and pre-clinical therapies in a demographic presentation view.

Only a hundred and fifty years have passed since Gregor Mendel’s discovery of simple Mendelian inheritance. In a remarkably short amount of time humans have achieved such impressive feats as sequencing the entire human genome and gaining understanding of the causes of most genetic disease. Now that researchers have all this information at hand, the focus has shifted to the design of reagents that can target specific genomic sequences. The rapid advancement of genome-editing techniques holds much promise for the field of human gene therapy. From bacteria to model organisms and human cells, genome editing tools such as zinc-finger nucleases (ZNFs), TALENs, and CRISPR/Cas9 have been successfully used to manipulate the respective genomes with unprecedented precision. With regard to human gene therapy, it is of great interest to test the feasibility of genome engineering because of their ease of customization and high-efficient site-specific cleavages that could potentially be used to treat a variety of human genetic disorders such as hemoglobinopathies, primary immunodeficiencies, and cancer.

Unraveling the potential of CRISPR-Cas9 for gene therapy

The molecular machinery from the prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)-Cas immune system has broadly been repurposed for genome editing in eukaryotes. In particular, the sequence-specific Cas9 endonuclease can be flexibly harnessed for the genesis of precise double-stranded DNA breaks, using single guide RNAs that are readily programmable. The endogenous DNA repair machinery subsequently generates genome modifications, either by random insertion or deletions using non-homologous end joining (NHEJ), or designed integration of mutations or genetic material using homology-directed repair (HDR) templates. This technology has opened new avenues for the investigation of genetic diseases in general, and for gene therapy applications in particular.

Patent Litigation over control of the revolutionary CRISPR-Cas9 tech

Despite the predicted utility of a successful gene editing technique, many current methods like Zinc Fingers Nucleases and TALENs have confounding issues like low efficiency, time-consuming procedures, and lack of specificity for both model organisms and humans. In the past several years, a new gene editing system viz, CRISPR-Cas9 derived from bacteria, has arisen as a frontrunner for efficient and successful gene editing.

Research in the area of CRISPR/Cas9 is gaining speed and this system could very well be the solution to many medical issues we face today. For evidence of CRISPR/Cas9’s promise, look no further than its attendant battle over intellectual property. Novartis and Atlas Venture joined together to form Editas Medicine, but a breakup of co-founders led Berkeley’s Jennifer Doudna to take her IP to the competing Intellia Therapeutics, while Swiss rival CRISPR Therapeutics has conflicting claims of its own backed by Versant. And now a team at Johns Hopkins has done some experiments to demonstrate its promise in engineering human stem cell therapies.

This proves that gene editing has staggering potential and that it can be developed as a naturalistic method of correcting defective genes by getting at the underlying causes of a broad range of diseases.

Gene Therapy’s fruition?

The world of gene therapy in which single-dose treatments correct debilitating defects enjoyed something of a renaissance in 2014. Strong clinical results from leaders in the once-maligned field spurred renewed optimism, helping a new generation of startups secure millions in venture financing to develop their next-generation approaches to the field. And that led to something of a trickle-up phenomenon in the industry, as the innovations of biotechs and academics convinced the world’s biggest players to give this field a second look. Now Bayer, Pfizer, Biogen Idec and Astellas are among the many companies toiling in gene therapy, joining high-profile biotechs like bluebird bio and uniQure.

DelveInsight’s Reports have already established a reputation of offering the affordable and comprehensive industry coverage and “on-the-ground” analysis in virtually every region of the world. These reports provide complete information for over 300 gene therapies which are in the pipeline for various therapy areas like; Oncology, Genitourinary, Dermatology, Central nervous system, Genetic Disorders, Hematological disorders, Metabolic disorders, Ophthalmology, Cardiovascular disease, Respiratory , Immunology, and many more…

DelveInsight’s Gene Therapy Reports cover the entire gene therapy market scenario including technology assessments, licensing opportunities, collaborations, market trends, pipeline coverage and competitive landscape. The report essentially provides DelveInsight’s proprietary market and pipeline analytics which identifies the front runners of all therapeutic areas. It also identifies the potential market movers and future regulatory landscape. These reports are designed to provide the clients with the means to out produce their competitors by developing a product that makes history.

For more info on Gene Therapy Reports for various Therapeutic areas contact us at: info@delveinsight.com.

Many companies have tried over the years to find a way to reverse the course of crippling neurodegenerative disorders like Huntington’s but have failed. Fortunately, Gene therapy has proven to be an answer to a wide range of serious neurodegenerative disorders like Huntington’s, and Parkinson’s etc.

The HD gene vs Gene Therapy

Huntington’s disease (HD) is an incurable, inherited disease entailing progressive loss of brain cells and motor function due to a defective gene (HD gene) which produces repeated copies of a defective protein called huntingtin, or mHTT which particularly damages a brain region called the striatum. About 30,000 Americans have Huntington’s disease (HD). Fortunately, Gene therapy which is a novel therapeutic branch of modern medicine has shown the potential for curing this disease by allowing the researchers to transfer genetic information into patient tissues and organs in order to eliminate or restore the normal functions of the diseased genes. A variety of gene therapy approaches have been tested in mouse models of HD, ranging from those aimed at ameliorating downstream pathology or replacing lost neuronal populations to more upstream strategies like gene silencing to reduce mHtt levels.

What’s already happening?

Companies like Genethon are working to provide effective treatment for curing Huntington’s disease through intrastriatal administration of a lentiviral vector carrying the gene hCNTF (Ciliary Neurotrophic Factor Human), a neuroprotective agent which protects striatal cells and maintains basal ganglia connectivity. This project is based upon ectopic expression of neurotrophic factors mediated by lentiviral vectors and is being conducted in partnership with Reference Centre for Huntington Disease as well as MIRCen (Molecular Imaging Research Center).

Another institute viz, The Children’s Hospital of Philadelphia’s (CHOP) gene therapy is also working on this disorder and recently experts have found a way to fine tune protein signals in order to provide significant relief for patients suffering from this disorder. This study is based upon adjusting the levels of a key signaling protein, in order to improve motor function and brain abnormalities in experimental animals with a form of Huntington’s disease. Neuroscientists already know that a signaling protein called mTORC1 regulates cell growth and metabolism and that it plays a key role in Huntington’s disease (HD). But the current study at The Children’s Hospital of Philadelphia’s (CHOP) Center for Cellular and Molecular Therapeutics contradicts the assumptions that inhibiting or shutting off the mTORC1 pathway, which interacts with the deleterious mHTT proteins, could help treat HD. Their study has shown that the mTORC1 pathway is already impaired in Huntington’s disease, and that improving this pathway’s functions can actually have a protective effect. However, restoring that pathway must be done very carefully as either too much or too little is detrimental. This proves that brain cells are capable of responding even after disease onset, and hints at the potential for reversing Huntington’s disease. (For details on this study, refer to http://www.ncbi.nlm.nih.gov/pubmed/25556834)

What’s hope and what’s hype?

Inspite of its checkered past gene therapy investigators in the 21st century agree that the field is enjoying a renaissance and that it has emerged with enormous potential in the field of Neurodegenerative disorders. Many companies like UniQure Biopharma, Sanofi, Oxford BioMedica etc., are operating in the field of Neurodegenerative disorders in the gene therapy domain. A growing number of partnership between companies in drug development for example between Audentes and Genethon etc., are driving the new gene therapy research. Thus leading to an increase in the global market opportunities for gene therapy with more companies focusing in this field.

DelveInsight’s Reportshave already established a reputation of offering the affordable and comprehensive industry coverage and “on-the-ground” analysis in virtually every region of the world. These reports provide complete information for over 300 gene therapies which are in the pipeline for various therapy areas like;Oncology, Genitourinary, Dermatology, Central nervous system, Genetic Disorders, Hematological disorders, Metabolic disorders, Ophthalmology, Cardiovascular disease, Respiratory , Immunology, and many more…

DelveInsight’s Gene Therapy Reports cover the entire gene therapy market scenario including technology assessments, licensing opportunities, collaborations, market trends, pipeline coverage and competitive landscape. The report essentially provides DelveInsight’s proprietary market and pipeline analytics which identifies the front runners of all therapeutic areas. It also identifies the potential market movers and future regulatory landscape. These reports are designed to provide the clients with the means to out produce their competitors by developing a product that makes history.

For more info on Gene Therapy Reports for various Therapeutic areas contact us at: info@delveinsight.com.

Gene Therapy: The “Big Value” Market!

Gene therapy has been under scientific research for over 2 decades, but viable therapies have yet to gain commercial acceptance due to safety and delivery-related issues. However, Pfizer’s move and some other recent developments in the industry suggest that the therapy may be coming off age. With the superlatively well-funded biotech Moderna Therapeutics raising another $450 million in venture cash, for its mRNA based proprietary approach to treat previously undruggable targets in a wide range of disease areas (with 45 preclinical programs in its pipeline), it has become clear that the Gene therapy market is going to be of great interest for many companies globally due to the possibility of a permanent cure that it offers for any of the more than 10,000 human diseases caused by a defect in a single gene.

About Gene Therapy

Gene therapy aims to fix a genetic problem at its source. By adding a corrected copy of a defective gene, gene therapy promises to help diseased tissues and organs work properly. This approach is different from traditional drug-based approaches, which may treat symptoms but not the underlying genetic problems. Put simply, it introduces a “good” gene into a person who has a disease caused by a “faulty” gene.

During the past two decades gene therapy has made important medical advances. Within this short time span, it has moved from the conceptual stage to technology development and laboratory research to clinical translational trials for a variety of deadly diseases. The researchers have learned from their mistakes and developed much more realistic approach and solutions to many of the problems which led to major clinical and commercial successes. It has become an upcoming research area in 21st century with the industry’s collective pipeline brimming with therapies close to 300.

There is a significant increase in the companies coming up with gene therapies for various therapeutic areas such as Novartis, GlaxoSmithKline, Sanofi, UniQure Biopharma, Oxford BioMedica etc., which are operating in the gene therapy domain. Moreover recent academic and industry partnerships for example between Celgene Corporation and Baylor College of Medicine, GSK and the Roswell Park Cancer Institute etc., are driving new gene therapy research.

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